Beyond the Blood: CSF-Derived cfDNA for Diagnosis and Characterization of CNS Tumors

Frontiers in Cell and Developmental Biology

Abbye E. McEwen¹  Christina M. Lockwood¹  Sarah E. S. Leary⁵ 

[1]Brotman Baty Institute for Precision Medicine, Seattle, WA, United States

[2]Department of Laboratory Medicine, University of Washington, Seattle, WA, United States

[3]Department of Pathology, University of Washington, Seattle, WA, United States

[4]Department of Pediatrics, University of Washington, Seattle, WA, United States

[5]Fred Hutchinson Cancer Research Center, Seattle, WA, United States

[6]Seattle Children’s Hospital, Cancer and Blood Disorders Center, Seattle, WA, United States

关键词: cell-free DNA;    cfDNA;    ctDNA;    liquid biopsy;    brain tumor;    biomarker;   

DOI  :  10.3389/fcell.2020.00045

来源: DOAJ

【 摘 要 】

Genetic data are rapidly becoming part of tumor classification and are integral to prognosis and predicting response to therapy. Current molecular tumor profiling relies heavily on tissue resection or biopsy. Tissue profiling has several disadvantages in tumors of the central nervous system, including the challenge associated with invasive biopsy, the heterogeneous nature of many malignancies where a small biopsy can underrepresent the mutational profile, and the frequent lack of obtaining a repeat biopsy, which limits routine monitoring to assess therapy response and/or tumor evolution. Circulating tumor, cell-free DNA (cfDNA), has been proposed as a liquid biopsy to address some limitations of tissue-based genetics. In cancer patients, a portion of cfDNA is tumor-derived and may contain somatic genetic alterations. In central nervous system (CNS) neoplasia, plasma tumor-derived cfDNA is very low or absent, likely due to the blood brain barrier. Interrogating cfDNA in cerebrospinal fluid (CSF) has several advantages. Compared to blood, CSF is paucicellular and therefore predominantly lacks non-tumor cfDNA; however, patients with CNS-limited tumors have significantly enriched tumor-derived cfDNA in CSF. In patients with metastatic CNS disease, mutations in CSF cfDNA are most concordant with the intracranial process. CSF cfDNA can also occasionally uncover additional genetic alterations absent in concurrent biopsy specimens, reflecting tumor heterogeneity. Although CSF is enriched for tumor-derived cfDNA, absolute quantities are low. Highly sensitive, targeted methods including next-generation sequencing and digital PCR are required to detect mutations in CSF cfDNA. Additional technical and bioinformatic approaches also facilitate enhanced ability to detect tumor mutations in CSF cfDNA.

【 授权许可】

Unknown